ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation， model， low- and high -dose （3.5 g·kg^-1 and 7 g·kg^-1） Rehmannia Radix Praeparata， and nimodipine （0.01 g·kg^-1） groups. The rat model of middle cerebral artery occlusion （MCAO） was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile， the serum levels of lactate dehydrogenase （LDH）， oxidative stress-related indicators superoxide dismutase （SOD）， glutathione peroxidase 4 （GPX4）， and malondialdehyde （MDA）， and the iron （Fe） content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats， Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector （beclin-1）， microtubule-associated protein light chain 3 （LC3B）， and ubiquitin-binding protein p62 （p62）. The ferroptosis-associated proteins included transferrin （TF）， transferrin receptor 1 （TFR1）， ferritin heavy chain 1 （FTH1）， and ferropotin （FPN1）. The neurological function injury-associated proteins included brain-derived neurotrophic factor （BDNF） and tyrosine kinase receptor B （TrkB）. ResultCompared with the sham operation group， the model group showed increased neurological function score， cerebral infarction volume， and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition， the model group presented elevated levels of LDH， MDA， and Fe （P<0.01） and lowered levels of SOD and GPX4 （P<0.01）. Compared with the model group， Rehmanniae Radix Praeparata decreased the content of LDH， MDA， and Fe （P<0.05， P<0.01） and elevated the levels of SOD and GPX4 （P<0.05， P<0.01）. Compared with the sham operation group， the modeling promoted the expression of beclin-1，LC3B Ⅱ/Ⅰ， TF， and TFR1 and inhibited the expression of p62， FTH1， FPN1， BDNF， and TrkB （P<0.01）. The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.

Objective:To investigate the diagnostic value of nucleic acid matrix-assisted laser desorption ionization-time of flight mass spectrometry（MALDI-TOF MS）in sputum smear-negative patients with nontuberculous Mycobacterial（NTM）pulmonary disease.Methods:Clinical data of 123 patients suspected of NTM pulmonary disease admitted in Public Health Clinical Center Affiliated to Shandong University between July 2022 and November 2023 were retrospectively analyzed. Bronchoalveolar lavage fluid（BALF）specimens were collected for MALDI-TOF MS assay and MGIT 960 culture. The diagnostic efficacy of MALDI-TOF MS for NTM pulmonary disease in patients with negative sputum smears for acid-fast bacilli was evaluated with receiver operating characteristic（ROC）curve. Statistical analysis was performed using SPSS 26.0 software and MedCalc statistical software.Results:Diagnosis of NTM pulmonary disease was finally confirmed in 66 out of the 123 suspected patients. It took 8 to 24 h for MALDI-TOF MS to identify NTM species and resistance. By MALDI-TOF MS，72 NTM strains were identified，with the Mycobacterium avium complex being the most prevalent（34 strains，47.22%），followed by the Mycobacterium abscessus complex（13 strains，18.06%）；resistance to macrolides was detected in 6 cases，while no resistance to aminoglycosides was found. It took 9 to 45 days for BALF MGIT 960 culture to identify NTM，and took 7 to 15 days for NTM typing and drug sensitivity testing. By BALF MGIT 960 culture，28 NTM strains were identified；and 1 case was found to be resistant to macrolides. Using confirmed diagnosis as the gold standard，MALDI-TOF MS demonstrated higher sensitivity，negative predictive value，and agreement rate compared to MGIT 960 culture（84.85% vs. 42.42%，81.13% vs. 56.32%，80.49% vs. 62.60%， χ2=25.667，8.998，9.664， P<0.05 or <0.01）. The area under ROC curve（AUC）for MALDI-TOF MS was significantly higher than that of MGIT 960 culture（0.801 vs. 0.642， Z=3.300， P=0.001）. Conclusion:Compared to MGIT 960 culture，MALDI-TOF MS exhibits superior diagnostic efficiency in detecting NTM pulmonary disease in patients with acid-fast bacilli smear-negative sputum，with advantage of rapidly identifying NTM species and resistance.

Objective To explore the independent risk factors that affect the overall survival(OS)of elderly patients with hepatocellular carcinoma(HCC,≥60 years old)and build a nomogram prediction model.Methods Clinical data of all elderly patients with HCC from the SEER database from 2005 to 2020 were downloaded from SEER database.In accordance with the inclusion and exclusion criteria,the screened patients were randomly assigned to a training group(70%)and a validation group(30%).The independent risk factors of elderly patients with HCC were determined by univariate and multivariate Cox regression analyses and further validated by Kaplan-Meier survival analysis.On the basis of the determined variables,nomograms were developed and verified to predict the OS of elderly patients with HCC at 6,12,and 24 months.The consistency index(C index),calibration curve,receiver's operating characteristic(ROC)curve,and area under curve(AUC)were used to evaluate the prediction efficiency and discrimination ability of the prediction model,and decision curve analysis(DCA)was used to evaluate the potential clinical application value of the nomogram.Results A total of 1134 elderly patients with HCC were included,with 793 in the training group and 341 in the validation group.Seven variables,including age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy,were identified as independent prognostic factors of this population.The constructed nomogram shows excellent prediction performance,with C indices of 0.745 in the training group and 0.704 in the validation group.The AUC values of the training group at 6,12,and 24 months were 0.785,0.788,and 0.798,respectively,and those of the validation group were 0.780,0.725,and 0.607,respectively.The calibration curve shows good consistency from the predicted survival probability to the actual probability.The ROC curve and DCA show that the nomogram proposed in this study has good prediction ability.Conclusion Age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy are important influencing factors for the survival of elderly patients with HCC.The prediction model of prognosis nomogram constructed in this study has good predictive value,and it can be used to predict the OS of elderly patients with HCC,which could be helpful for individualized survival assessment and clinical management of these patients.

Objective:To calculate the scale of China's mental health treatment costs,analyze its financing structure,and provide a decision-making basis for optimizing China's mental health disease financing,prevention and control policies.Methods:System of Health Account 2011 was employed to calculate mental disorders(MDs)curative expenditure,and analyze the expenditure by health function,health provider and financing schemes.Results:In 2018,MDs curative expenditure in China was 87.17 billion yuan.Of MDs curative expenditure,over 84%occurred in hospitals,and over 66%was spent on inpatient care.31.80%of MDs curative expenditure was financed by Out-of-Pocket(OOP).Conclusion:China's mental health and mental disorders treatment costs are developing rapidly,the existing resource allocation is unreasonable,and there is an urgent need to optimize the function and institutional configuration.MDs patients and their families bare a high burden on MDs curative expenditure,and the financing policy needs to be further improved.

Background Pesticide exposure may impact the reproductive health of women undergoing assisted reproductive technology (ART). However, data on pesticide exposure levels in women undergoing ART in China are scarce, and current research on influencing factors is limited. Objective To evaluate the preconceptional pesticide exposure levels and identify potential determinants among women undergoing ART. Methods This study was designed as a cross-sectional survey and recruited 508 women undergoing ART from July 2017 to December 2018 at the fertility clinic of the International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Gas chromatography/liquid chromatography-tandem mass spectrometry was used to determine the metabolite concentrations of organophosphate pesticides (OPs), pyrethroid pesticides (PYRs), and neonicotinoid pesticides (NEOs) in urine. The sum of molar concentrations of the three pesticide classes (∑₂OPs, ∑₂PYRs, and ∑₂NEOs) were calculated. A questionnaire was used to collect demographic characteristics, dietary habits, and behavioral information. Multiple linear regression was employed to analyze the associations of demographic characteristics, dietary habits, and behavioral variables with the concentrations of pesticide metabolites in urine among the participants. Results The median creatinine-adjusted concentrations of ∑₂OPs, ∑₂PYRs, and ∑₂NEOs in this study were 419.77, 2.95, and 20.36 nmol·g⁻¹, respectively. The multiple linear regression results showed that the urinary concentration of ∑₂OPs was 42.88% higher in the participants with daily vegetable intake than in those who consumed vegetables ≤3 d per week (P<0.05), and the urinary concentration of ∑₂PYRs was 37.24% higher in the participants with daily fruit intake than in those who consumed fruits ≤3 d per week (P<0.01). Similarly, the urinary concentrations of ∑₂NEOs were 24.51% and 29.30% higher in the participants who consumed fruits daily and 4-6 d per week, respectively, than in those who consumed fruits ≤3 d per week (P<0.05). Besides, we also found that the urinary concentration of ∑₂PYRs was negatively correlated with body mass index (BMI) in the participants (P<0.05). Furthermore, the urinary concentration of ∑₂NEOs was not only positively correlated with age (P<0.05), but also significantly associated with pet ownership and infertility causes among the participants. Specifically, the participants who continued to own pets after conception had a 30.11% higher urinary concentration of ∑₂NEOs than those who never owned pets (P<0.05), and the participants with infertility due to female factors had a 24.10% lower urinary concentration of ∑₂NEOs than those who received ART treatment for infertility caused by male factors (P<0.05). Conclusion The women undergoing ART in Shanghai are widely exposed to pesticides. Age, BMI, frequency of vegetable and fruit intake, pet ownership, and infertility causes may be related to the pesticide exposure levels in this population. However, more human data are needed to confirm these findings.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective To use the cognitive reinforcement comprehensive intervention program constructed by our team to intervene in patients with spinal cord injury and evaluate its clinical application effect.Methods A non-randomized trial design was adopted to select 97 patients with spinal cord injury from November 2021 to September 2022.Forty-four patients from March to September 2022 in a Grade A hospital in Hefei City were included in the experimental group,and 53 patients from November 2021 to February 2022 were included in the control group.The cognitive reinforcement comprehensive intervention program was used to intervene in the experimental group,and the conventional rehabilitation nursing was used to intervene in the control group.The intervention lasted for 12 weeks in both groups.The Changsha Montreal Scale,Social Support Rating Scale,Rehabilitation Exercise Self-efficacy Scale,Spinal Cord Injury Independence Rating Scale and Hamilton Anxiety Scale were used to measure the two groups before intervention,1 month after intervention and 3 months after intervention.Results 40 cases in the experimental group and 48 cases in the control group completed the study.Repeated measurement ANOVA showed that the temporal,interactive and intergroup effects of cognitive function scores and anxiety scores were statistically significant(P＜0.05).The time effect and interaction effect of the subjective support dimension score,coping self-efficacy dimension score of the two groups were statistically significant(P＜0.05).One month after the intervention,the cognitive function scores of test group were higher than before intervention and control group,and the anxiety scores were lower than before intervention and control group(P＜0.05).Three months after the intervention,the scores of cognitive function,subjective support dimension and coping self-efficacy dimension of experimental group were higher than those before intervention and control group,and the scores of anxiety level were lower than those before intervention and control group(P＜0.05).Conclusion Comprehensive intervention of cognitive reinforcement can improve the cognitive function of patients with spinal cord injury,delay the process of cognitive impairment,enhance self-confidence,relieve anxiety,and promote physical and mental rehabilitation of patients.

Objective:To investigate the value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) parameters combined with T 2WI texture analysis of primary lesions of rectal adenocarcinoma in preoperative prediction of lymph node metastasis with short diameter ≤9 mm. Methods:Retrospective analysis was performed on 115 cases of rectal adenocarcinoma confirmed by surgical pathology in Affiliated Provincial Hospital of Anhui Medical University from June 2015 to October 2020. All patients underwent total mesorectal resection and received conventional rectal MRI and IVIM-DWI scan before surgery. According to the pathological results of lymph node, the patients were divided into lymph node metastatic group ( n=44) and non-metastatic group ( n=71). IVIM-DWI parameters of primary rectal adenocarcinoma were measured including apparent diffusion coefficient (ADC), diffusion coefficient (D), pseudo diffusion coefficient (D *) and perfusion fraction (f). The region of interest (ROI) of the whole lesion of rectal adenocarcinoma was delineated on axial T 2WI; then the ROIs were imported into GE Analysis Kit software to extract 3D texture feature. The differences of IVIM-DWI parameters and texture feature parameters were compared between two groups using independent sample t test or Mann-Whitney U test. The optimal texture feature parameters with independent predictive function were screened by multivariate logistic regression. Then the texture feature model and combined model based IVIM-DWI and texture feature parameters were established. The receiver operating characteristic (ROC) curves were used to evaluate the performances of IVIM-DWI, texture feature parameters, texture feature model and combined model in predicting lymph node metastasis in patients with rectal adenocarcinoma. The area under the ROC curve (AUC) were compared with DeLong test. Results:Among all the IVIM-DWI parameters, the D * and f values of primary rectal adenocarcinoma were significantly different between the lymph node metastasis group and the non-lymph node metastasis group ( Z=3.39, P=0.001, Z=-3.06, P=0.002); no statistical significance was found in the ADC and D values between two groups (both P>0.05). A total of 828 texture feature parameters were obtained based on T 2WI of primary lesion of rectal adenocarcinoma, among which 3 optimal texture feature parameters were selected, including firstorder_Skewness, shape_Sphericity and glcm_Idn. The ROC curve results showed that the AUC of D * and f were 0.689 and 0.670, respectively. The AUC of 3 texture feature parameters were 0.651, 0.628, 0.631, respectively. The AUC of texture feature model and the combined model were 0.775 and 0.803. The AUC of combined model was larger than D *, f and the three texture feature parameters (all P<0.05). Conclusion:IVIM-DWI parameters combined with T 2WI texture feature parameters in primary lesion of rectal adenocarcinoma show good diagnostic efficacy in preoperative prediction of lymph node metastasis with short diameter≤9 mm.

Objective:To investigate expressions and clinical significance of plasma exosomal hsa_circ_0022417 in gastric cancer (GC).Methods:Sixty gastric cancer patients, 30 chronic gastritis patients (disease control group) and 30 healthy volunteers (healthy control group) were enrolled in this study. The expression levels of plasma exosomal hsa_circ_0022417 and serum CEA and CA19-9 were detected. The ROC curve and AUC were used to estimate the diagnostic capacity.Results:Compared with chronic gastritis patients and healthy control, the expression of plasma exosomal hsa_circ_0022417 was significantly upregulated in the gastric cancer group ( F=9.96, P<0.05). The expression level of hsa_circ_0022417 in GC tissue was significantly higher than that in adjacent tissue ( t=6.08, P<0.05). The AUC of hsa_circ_0022417, serum CEA and CA 19-9 was 0.79, 0.68 and 0.66, respectively. The combined detection of three indicators had the highest AUC (0.86) ( P<0.05). The expression level of exosomal hsa_circ_0022417 was significantly correlated with tumor size ( χ2=6.42, P<0.01), differentiation degree ( χ2=5.83, P=0.05), TNM stage ( χ2=7.14, P<0.05) and lymph node metastasis ( χ2=5.17, P<0.05). Conclusion:Exosome hsa_circ_0022417 is highly expressed in the plasma of GC patients, which is of great significance for clinical auxiliary diagnosis and early screening of GC.